Tolerability of IM penicillin G benzathine diluted or not with local anesthetics, or different gauge needles for syphilis treatment: a randomized clinical trial.
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ABSTRACT:
SUBMITTER: Estrada V
PROVIDER: S-EPMC6813081 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo estimate the risk of serious adverse reactions to benzathine penicillin in pregnant women for preventing congenital syphilis.MethodsWe searched for clinical trials or cohorts that assessed the incidence of serious adverse reactions to benzathine penicillin in pregnant women and the general population (indirect evidence). MEDLINE, EMBASE, Scopus and other databases were searched up to December 2012. The GRADE approach was used to assess quality of evidence. Absolute risks of each study were calculated along with their 95% confidence intervals (95% CI). We employed the DerSimonian and Laird random effects model in the meta-analyses.ResultsFrom 2,765 retrieved studies we included 13, representing 3,466,780 patients. The studies that included pregnant women were conducted to demonstrate the effectiveness of benzathine penicillin: no serious adverse reactions were reported among the 1,244 pregnant women included. In the general population, among 2,028,982 patients treated, 4 died from an adverse reaction. The pooled risk of death was virtually zero. Fifty-four cases of anaphylaxis were reported (pooled absolute risk = 0.002%; 95% CI: 0%-0.003% I(2) = 12%). From that estimate, penicillin treatment would be expected to result in an incidence of 0 to 3 cases of anaphylaxis per 100,000 treated. Any adverse reactions were reported in 6,377 patients among 3,465,322 treated with penicillin (pooled absolute risk = 0.169%; 95% CI: 0.073%-0.265% I(2) = 97%). The quality of evidence was very low.ConclusionStudies that assessed the risk of serious adverse events due to benzathine penicillin treatment in pregnant women were scarce, but no reports of adverse reactions were found. The incidence of severe adverse outcomes was very low in the general population. The risk of treating pregnant women with benzathine penicillin to prevent congenital syphilis appears very low and does not outweigh its benefits. Further research is needed to improve the quality of evidence.
| S-EPMC3578834 | biostudies-literature
Project description:BackgroundThe shortage of benzathine penicillin G (BPG) worldwide presents a major challenge in the treatment of syphilis. Its availability for syphilis treatment has not been adequately evaluated in China.MethodsTwo surveys were conducted among hospitals providing sexually transmitted infection clinical services in Shandong Province in 2012 and 2018. Data on the basic information and BPG availability of the surveyed hospitals and related factors were collected and analyzed using SPSS 17.0.ResultsA total of 433 and 515 hospitals were surveyed in 2012 and 2018, respectively. A significant difference in BPG availability was observed among different levels and types of hospitals both in 2012 (X2 = 9.747, p = 0.008; X2 = 37.167, p = 0.000) and 2018 (X2 = 11.775, p = 0.003; X2 = 28.331, p = 0.000). The BPG availability among surveyed hospitals increased from 45.0% in 2012 to 56.4% in 2018 (X2 = 11.131, p = 0.001). The BPG availability was higher in 2018 than in 2012 among county-level hospitals (52.0% vs. 40.8%, X2 = 7.783, p = 0.005), general western medicine hospitals (62.1% vs. 50.0%, X2 = 6.742, p = 0.009), maternal and child health hospitals (57.1% vs. 26.9%, X2 = 13.906, p = 0.000), and public hospitals (56.8% vs. 45.0%, X2 = 11.361, p = 0.001). However, the county-level availability of BPG (at least one hospital has BPG in a county-level unit) has not improved between 2012 and 2018 (65.93% vs. 70.34%; X2 = 0.563, p = 0.453). The absences of clinical needs, restriction of clinical antibacterial drugs, and lack of qualifications for providing syphilis treatment were the major reasons for the low BPG availability of hospitals.ConclusionsBPG availability for syphilis treatment in Shandong Province remains low and presents disparities among different levels and types of hospitals, although it has been improved in recent years. The low availability of BPG for syphilis treatment in China is related to its clinical use by doctors rather than the market supply. Health care reforms should further improve the availability and accessibility of health services.
| S-EPMC6431030 | biostudies-literature
Project description:BackgroundTreatment guidelines recommend the use of a single dose of benzathine penicillin G (BPG) for treating early syphilis in human immunodeficiency virus (HIV)-infected persons. However, data supporting this recommendation are limited. We examined the efficacy of single-dose BPG in the US Military HIV Natural History Study.MethodsSubjects were included if they met serologic criteria for syphilis (ie, a positive nontreponemal test [NTr] confirmed by treponemal testing). Response to treatment was assessed at 13 months and was defined by a ≥4-fold decline in NTr titer. Multivariate Cox proportional hazard regression models were utilized to examine factors associated with treatment response.ResultsThree hundred fifty subjects (99% male) contributed 478 cases. Three hundred ninety-three cases were treated exclusively with BPG (141 with 1 dose of BPG). Treatment response was the same among those receiving 1 or >1 dose of BPG (92%). In a multivariate analysis, older age (hazard ratio [HR], 0.82 per 10-year increase; 95% confidence interval [CI], .73-.93) was associated with delayed response to treatment. Higher pretreatment titers (reference NTr titer <1:64; HR, 1.94 [95% CI, 1.58-2.39]) and CD4 counts (HR, 1.07 for every 100-cell increase [95% CI, 1.01-1.12]) were associated with a faster response to treatment. Response was not affected by the number of BPG doses received (reference, 1 dose of BPG; HR, 1.11 [95% CI, .89-1.4]).ConclusionsIn this cohort, additional BPG doses did not affect treatment response. Our data support the current recommendations for the use of a single dose of BPG to treat HIV-infected persons with early syphilis.
| S-EPMC6477935 | biostudies-literature
Project description:BackgroundWHO recommends use of rapid dual HIV/syphilis tests for screening pregnant women (PW) during antenatal care to prevent mother-to-child transmission. Scale-up of testing implies a need to accurately forecast and procure benzathine penicillin (BPG) to treat the additionally identified PW with syphilis.MethodsCountry-reported ANC coverage, PW syphilis screening and treatment coverage values in 2019 were scaled linearly to EMTCT targets by 2030 (constant increasing slope from 2019 figures to 95% in 2030) for 11 focus countries. Antenatal syphilis screening coverage was substituted with HIV screening coverage to estimate potential contribution of rapid dual HIV/syphilis tests in identifying additional PW with syphilis. BPG demand was calculated for 2019-2030 accordingly.ResultsThe estimated demand for BPG (in 2.4 million unit vials) using current maternal syphilis prevalence and treatment coverage will increase from a baseline of 414,459 doses in 2019 to 683,067 doses (+65%) in 2021 assuming immediate replacement of single HIV test kits with rapid dual HIV/syphilis tests for these 11 countries. Continued scale up of syphilis screening and treatment coverage to reach elimination coverage of 95% will result in an estimated demand increase of 160%, (663,969 doses) from 2019 baseline for a total demand of 1,078,428 BPG doses by 2030.ConclusionsDemand for BPG will increase following adoption of rapid dual HIV/syphilis test kits due to increases in maternal diagnoses of syphilis. To eliminate congenital syphilis, MNCH clinical programs will need to synergize with disease surveillance programs to accurately forecast BPG demand with scale up of antenatal syphilis screening to ensure adequate treatment is available for pregnant women diagnosed with syphilis.
| S-EPMC8376004 | biostudies-literature
Project description:BACKGROUND:Benzathine penicillin G (BPG) is the only recommended treatment to prevent mother-to-child transmission of syphilis. Due to recent reports of country-level shortages of BPG, an evaluation was undertaken to quantify countries that have experienced shortages in the past 2 years and to describe factors contributing to these shortages. METHODS AND FINDINGS:Country-level data about BPG shortages were collected using 3 survey approaches. First, a survey designed by the WHO Department of Reproductive Health and Research was distributed to 41 countries and territories in the Americas and 41 more in Africa. Second, WHO conducted an email survey of 28 US Centers for Disease Control and Prevention country directors. An additional 13 countries were in contact with WHO for related congenital syphilis prevention activities and also reported on BPG shortages. Third, the Clinton Health Access Initiative (CHAI) collected data from 14 countries (where it has active operations) to understand the extent of stock-outs, in-country purchasing, usage behavior, and breadth of available purchasing options to identify stock-outs worldwide. CHAI also conducted in-person interviews in the same 14 countries to understand the extent of stock-outs, in-country purchasing and usage behavior, and available purchasing options. CHAI also completed a desk review of 10 additional high-income countries, which were also included. BPG shortages were attributable to shortfalls in supply, demand, and procurement in the countries assessed. This assessment should not be considered globally representative as countries not surveyed may also have experienced BPG shortages. Country contacts may not have been aware of BPG shortages when surveyed or may have underreported medication substitutions due to desirability bias. Funding for the purchase of BPG by countries was not evaluated. In all, 114 countries and territories were approached to provide information on BPG shortages occurring during 2014-2016. Of unique countries and territories, 95 (83%) responded or had information evaluable from public records. Of these 95 countries and territories, 39 (41%) reported a BPG shortage, and 56 (59%) reported no BPG shortage; 10 (12%) countries with and without BPG shortages reported use of antibiotic alternatives to BPG for treatment of maternal syphilis. Market exits, inflexible production cycles, and minimum order quantities affect BPG supply. On the demand side, inaccurate forecasts and sole sourcing lead to under-procurement. Clinicians may also incorrectly prescribe BPG substitutes due to misperceptions of quality or of the likelihood of adverse outcomes. CONCLUSIONS:Targets for improvement include drug forecasting and procurement, and addressing provider reluctance to use BPG. Opportunities to improve global supply, demand, and use of BPG should be prioritized alongside congenital syphilis elimination efforts.
| S-EPMC5744908 | biostudies-literature
Project description:IntroductionPoorer serologic responses of early syphilis to treatment have been inconsistently reported in HIV-positive patients compared with HIV-negative patients, but the interpretation of previous studies is limited by discrepant study designs. The present study aimed to evaluate the effect of HIV infection on the treatment response to a single dose of benzathine penicillin G (BPG) for early syphilis.MethodsFrom January 2015 to March 2020, adult patients with early syphilis who received a single dose of BPG were enrolled and rapid plasma reagin (RPR) titers were periodically determined. The primary outcome was serologic response, defined as at least a fourfold decline of RPR titer at 12 months of BPG treatment compared with that at baseline, which was examined in the intention-to-treat (ITT) and per-protocol analyses. Treatment failure included lack of at least a fourfold decline in RPR titers and at least a fourfold increase in RPR titers.ResultsWe prospectively enrolled 184 HIV-positive and 68 HIV-negative participants with early syphilis, who were all men who have sex with men, with a higher proportion of previous syphilis (70.1%) and early latent syphilis (64.1%) among HIV-positive participants. In the ITT with last-observation-carried-forward analysis, HIV-positive participants had a significantly lower serologic response rate at 12 months of treatment than HIV-negative participants (73.4% vs. 91.2%). Of HIV-positive participants, 12.5% failed to achieve at least fourfold decline in RPR titers and 14.1% had at least a fourfold increase in RPR titers. The factors associated with 12-month serologic response were HIV infection (adjusted odds ratio [AOR] 0.33; 95% confidence interval [CI] 0.13-0.81) and RPR titer (per 1-log2 increase, AOR 1.36; 95% CI 1.23-1.51).ConclusionHIV-positive patients with early syphilis had poorer serologic responses to BPG treatment than HIV-negative patients during a 12-month follow-up period.
| S-EPMC8322187 | biostudies-literature
Project description:Benzathine penicillin G (BPG) is used as first-line treatment for most forms of syphilis and as secondary prophylaxis against rheumatic heart disease (RHD). Perceptions that poor quality of BPG is linked to reported adverse effects and therapeutic failure may impact syphilis and RHD control programs. Clinical networks and web-based advertising were used to obtain vials of BPG from a wide range of countries. The quality of BPG was assessed using a high performance liquid chromatography assay capable of detecting relevant impurities and degradation products. Tests for water content, presence of heavy metals and physical characteristics of BPG, including particle size analysis and optical microscopy, also were conducted. Thirty-five batches of BPG were sourced from 16 countries across 4 WHO regions. All batches passed the US Pharmacopeia requirements for BPG injection (content), with no evidence of breakdown products or other detected contaminants. Water content and heavy metal analysis (n = 11) indicated adherence to regulatory standards and Good Manufacturing Practice. Particle size analysis (n = 20) found two batches with aggregated particles (>400 µm) that were dispersed following sonication. Current batches of BPG were of satisfactory pharmaceutical quality but aggregated particles were found in a modest proportion of samples. Future studies should focus on the physical characteristics of BPG which may contribute to variations in plasma penicillin concentrations an observed needle blockages in clinical practice. Pharmacopeial monographs could be revised to include standards on particle size and crystal morphology of BPG.
| S-EPMC7580708 | biostudies-literature
Project description:BackgroundOne dose of benzathine penicillin G (BPG) has been recommended for HIV-infected patients with early syphilis (primary, secondary, and early latent syphilis) in the sexually transmitted diseases treatment guidelines, but clinical data to support such a recommendation are limited.MethodsWe prospectively observed the serological response to 1 or 3 weekly doses of BPG in HIV-infected adults who sought treatment of early syphilis at 8 hospitals around Taiwan. Rapid plasma reagin (RPR) titers were followed every 3-6 months after treatment. The serological response was defined as a 4-fold or greater decline in RPR titers at 12 months of treatment. The missing values were treated by following the last-observed-carried-forward principle. We hypothesized that 1 dose was non-inferior to 3 weekly doses of BPG with the non-inferiority margin for the difference of serological response set to 10%.ResultsBetween 2007 and 2012, 573 patients completed at least 12 months of follow-up: 295 (51.5%) receiving 1 dose of BPG (1-dose group) and 278 (48.5%) 3 doses (3-dose group). Overall, 198 patients (67.1%; 95% confidence interval [CI], 61.4-72.5%) in the 1-dose group achieved serological response at 12 months, as did 208 patients (74.8%; 95% CI, 69.3-79.8%) in the 3-dose group (one-sided 95% CI of the difference, 15.1%). In the multivariate analysis, secondary syphilis (adjusted odds ratio [AOR], 1.90; 95% CI 1.17-3.09), RPR titer ?32 (AOR, 1.93; 95% CI, 1.38-2.69), and 3 doses of BPG (AOR, 1.68; 95% CI, 1.20-2.36) were independently associated with a serological response. The time to the first episode of treatment failure was 1184 (standard deviation [SD], 70.5) and 1436 (SD, 80.0) days for 1- and 3-dose group, respectively.ConclusionsSingle-dose BPG resulted in a higher serological failure rate and shorter time to treatment failure than 3 weekly doses of BPG in the treatment of early syphilis in HIV-infected patients.
| S-EPMC4186862 | biostudies-literature
Project description:BackgroundWhile doxycycline is recommended as an alternative treatment of syphilis in patients with penicillin allergy or intolerance, clinical studies to compare serological response to doxycycline versus benzathine penicillin in treatment of early syphilis among HIV-infected patients remain sparse.MethodsWe retrospectively reviewed the medical records of HIV-infected patients with early syphilis who received doxycycline 100 mg twice daily for 14 days (doxycycline group) and those who received 1 dose of benzathine penicillin (2.4 million units) (penicillin group) between 2007 and 2013. Serological responses defined as a decline of rapid plasma reagin titer by 4-fold or greater at 6 and 12 months of treatment were compared between the two groups.ResultsDuring the study period, 123 and 271 patients in the doxycycline and penicillin group, respectively, completed 6 months or longer follow-up. Ninety-one and 271 patients in the doxycycline and penicillin group, respectively, completed 12 months or longer follow-up. Clinical characteristics were similar between the two groups, except that, compared with penicillin group, doxycycline group had a lower proportion of patients with secondary syphilis (65.4% versus 41.5%, P<0.0001) and a higher proportion of patients with early latent syphilis (25.3% versus 49.6%, P<0.0001). No statistically significant differences were found in the serological response rates to doxycycline versus benzathine penicillin at 6 months (63.4% versus 72.3%, P?=?0.075) and 12 months of treatment (65.9% versus 68.3%, P?=?0.681). In multivariate analysis, secondary syphilis, but not treatment regimen, was consistently associated with serological response at 6 and 12 months of follow-up.ConclusionsThe serological response rates to a 14-day course of doxycycline and a single dose of benzathine penicillin were similar in HIV-infected patients with early syphilis at 6 and 12 months of follow-up. Patients with secondary syphilis were more likely to achieve serological response than those with other stages.
| S-EPMC4195693 | biostudies-literature
Project description:BACKGROUND AND STUDY AIMS: 19-gauge (19G) needles are used for EUS-guided tissue acquisition and interventions. The aim of the current study was to compare the functional characteristics of 19G EUS needles by means of using various echoendoscopes in a bench simulator. METHODS: The angles achieved for 19G needles (EchoTip: ET-19G, EchoTip Flex: ExF-19G, Expect: Ex-19G, and ProCore: PC-19G) and for the distal tip of the echoendoscope were evaluated for maximal angulation settings of the distal tip and the elevator. Also the resistance to advancement of the 19G needles at these endoscope settings was assessed. All evaluations were done with endoscopes in a straight and in a curved position. RESULTS: There was no large discrepancy for scope and needle angles among all echoendoscopes except for the slim Pentax scope (EG-3270UK). The ExF-19G and PC-19G needles showed better optimal angles in various conditions compared to standard 19G needles. In straight scope position, out of the 20 conditions (5 endoscopes × 2 positions of the distal tip × 2 elevator positions) the numbers of optimal angulations achieved for the Ex-19G, ExF-19G, ET-19G, and PC-19G, were 11 /20 (55 %), 20 /20 (100 %), 14 /20 (70 %) and 18 /20 (90 %), respectively. However, regarding resistance, it was impossible to advance theneedle with 14 /20 settings (70 %) for the Ex-19G, 3 /20 (15 %) for the ExF-19G, 10 /20 (50 %) for the ET-19G and 7 /20 (35 %) for the PC-19G. When the scopes were bent, with regard to the force needed to advance the needle, the numbers of optimal settings, for the Ex-19G, ExF-19G, ET-19G, and PC-19G, were 1 (5 %), 13 (65 %), 6 (30 %) and 8 (40 %), respectively. The mean maximum resistance to advancement was less for the ExF-19G than for the other needless in almost all scope and angle conditions (p < 0.05). CONCLUSION: Although there was no difference between needles, the resistance to passage was least with the flexible 19-gauge needle (ExF-19G).
| S-EPMC4440372 | biostudies-other